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Q99741

- CDC6_HUMAN

UniProt

Q99741 - CDC6_HUMAN

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Protein

Cell division control protein 6 homolog

Gene

CDC6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi202 – 2098ATPSequence Analysis

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. chromatin binding Source: Ensembl
  3. kinase binding Source: BHF-UCL
  4. nucleotide binding Source: ProtInc

GO - Biological processi

  1. DNA replication Source: Reactome
  2. DNA replication checkpoint Source: ProtInc
  3. G1/S transition of mitotic cell cycle Source: Reactome
  4. mitotic cell cycle Source: Reactome
  5. mitotic nuclear division Source: UniProtKB-KW
  6. negative regulation of cell proliferation Source: ProtInc
  7. negative regulation of DNA replication Source: ProtInc
  8. positive regulation of chromosome segregation Source: BHF-UCL
  9. positive regulation of cytokinesis Source: BHF-UCL
  10. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
  11. regulation of mitotic metaphase/anaphase transition Source: BHF-UCL
  12. regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
  13. traversing start control point of mitotic cell cycle Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, DNA replication, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_1095. Activation of the pre-replicative complex.
REACT_111214. G0 and Early G1.
REACT_1156. Orc1 removal from chromatin.
REACT_1181. Association of licensing factors with the pre-replicative complex.
REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
REACT_1707. CDC6 association with the ORC:origin complex.
REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
REACT_207. Removal of licensing factors from origins.
REACT_2243. Assembly of the pre-replicative complex.
REACT_471. E2F mediated regulation of DNA replication.
REACT_6769. Activation of ATR in response to replication stress.
REACT_683. G1/S-Specific Transcription.
SignaLinkiQ99741.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell division control protein 6 homolog
Alternative name(s):
CDC6-related protein
Cdc18-related protein
Short name:
HsCdc18
p62(cdc6)
Short name:
HsCDC6
Gene namesi
Name:CDC6
Synonyms:CDC18L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:1744. CDC6.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication
Note: The protein is nuclear in G1 and cytoplasmic in S-phase cells.

GO - Cellular componenti

  1. cytoplasm Source: HPA
  2. cytosol Source: Reactome
  3. Golgi apparatus Source: HPA
  4. nucleoplasm Source: Reactome
  5. nucleus Source: BHF-UCL
  6. spindle midzone Source: BHF-UCL
  7. spindle pole Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Meier-Gorlin syndrome 5 (MGORS5) [MIM:613805]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti323 – 3231T → R in MGORS5. 1 Publication
VAR_065493

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MIMi613805. phenotype.
Orphaneti2554. Ear-patella-short stature syndrome.
PharmGKBiPA26271.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 560560Cell division control protein 6 homologPRO_0000150979Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei45 – 451Phosphoserine1 Publication
Modified residuei54 – 541Phosphoserine1 Publication
Modified residuei127 – 1271Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ99741.
PaxDbiQ99741.
PRIDEiQ99741.

PTM databases

PhosphoSiteiQ99741.

Miscellaneous databases

PMAP-CutDBQ99741.

Expressioni

Gene expression databases

BgeeiQ99741.
CleanExiHS_CDC6.
ExpressionAtlasiQ99741. baseline and differential.
GenevestigatoriQ99741.

Organism-specific databases

HPAiHPA050114.
HPA054703.

Interactioni

Subunit structurei

Interacts with PCNA, ORC1L, cyclin-CDK and HUWE1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDKN1AP389362EBI-374862,EBI-375077
CDT1Q9H2113EBI-374862,EBI-456953
MCM7P339932EBI-374862,EBI-355924

Protein-protein interaction databases

BioGridi107426. 49 interactions.
DIPiDIP-28154N.
IntActiQ99741. 21 interactions.
MINTiMINT-1201847.
STRINGi9606.ENSP00000209728.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CCHX-ray1.70E/F89-100[»]
2CCIX-ray2.70F/I71-100[»]
4I5LX-ray2.43B/E70-90[»]
4I5NX-ray2.80B/E70-90[»]
ProteinModelPortaliQ99741.
SMRiQ99741. Positions 279-320.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99741.

Family & Domainsi

Sequence similaritiesi

Belongs to the CDC6/cdc18 family.Curated

Phylogenomic databases

eggNOGiCOG1474.
GeneTreeiENSGT00530000063498.
HOGENOMiHOG000045316.
HOVERGENiHBG050860.
InParanoidiQ99741.
KOiK02213.
OMAiPYTRNQI.
OrthoDBiEOG7QG44J.
PhylomeDBiQ99741.
TreeFamiTF101051.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003593. AAA+_ATPase.
IPR015163. Cdc6_C_dom.
IPR016314. Cell_div_Cdc6/18.
IPR027417. P-loop_NTPase.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF09079. Cdc6_C. 1 hit.
[Graphical view]
PIRSFiPIRSF001767. Cdc6. 1 hit.
SMARTiSM00382. AAA. 1 hit.
SM01074. Cdc6_C. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

Q99741-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPQTRSQAQA TISFPKRKLS RALNKAKNSS DAKLEPTNVQ TVTCSPRVKA
60 70 80 90 100
LPLSPRKRLG DDNLCNTPHL PPCSPPKQGK KENGPPHSHT LKGRRLVFDN
110 120 130 140 150
QLTIKSPSKR ELAKVHQNKI LSSVRKSQEI TTNSEQRCPL KKESACVRLF
160 170 180 190 200
KQEGTCYQQA KLVLNTAVPD RLPAREREMD VIRNFLREHI CGKKAGSLYL
210 220 230 240 250
SGAPGTGKTA CLSRILQDLK KELKGFKTIM LNCMSLRTAQ AVFPAIAQEI
260 270 280 290 300
CQEEVSRPAG KDMMRKLEKH MTAEKGPMIV LVLDEMDQLD SKGQDVLYTL
310 320 330 340 350
FEWPWLSNSH LVLIGIANTL DLTDRILPRL QAREKCKPQL LNFPPYTRNQ
360 370 380 390 400
IVTILQDRLN QVSRDQVLDN AAVQFCARKV SAVSGDVRKA LDVCRRAIEI
410 420 430 440 450
VESDVKSQTI LKPLSECKSP SEPLIPKRVG LIHISQVISE VDGNRMTLSQ
460 470 480 490 500
EGAQDSFPLQ QKILVCSLML LIRQLKIKEV TLGKLYEAYS KVCRKQQVAA
510 520 530 540 550
VDQSECLSLS GLLEARGILG LKRNKETRLT KVFFKIEEKE IEHALKDKAL
560
IGNILATGLP
Length:560
Mass (Da):62,720
Last modified:May 1, 1997 - v1
Checksum:i3ED7DE4AF80CB017
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti238 – 2381T → A.1 Publication
Corresponds to variant rs4135010 [ dbSNP | Ensembl ].
VAR_019349
Natural varianti295 – 2951D → N.1 Publication
Corresponds to variant rs4135012 [ dbSNP | Ensembl ].
VAR_019350
Natural varianti299 – 2991T → M.1 Publication
Corresponds to variant rs4135013 [ dbSNP | Ensembl ].
VAR_019351
Natural varianti323 – 3231T → R in MGORS5. 1 Publication
VAR_065493
Natural varianti378 – 3781R → H.1 Publication
Corresponds to variant rs4135016 [ dbSNP | Ensembl ].
VAR_019352
Natural varianti441 – 4411V → I.2 Publications
Corresponds to variant rs13706 [ dbSNP | Ensembl ].
VAR_019353

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77949 mRNA. Translation: AAB38317.1.
AF022109 mRNA. Translation: AAC52071.1.
AY150310 Genomic DNA. Translation: AAN10296.1.
BC025232 mRNA. Translation: AAH25232.1.
CCDSiCCDS11365.1.
RefSeqiNP_001245.1. NM_001254.3.
UniGeneiHs.405958.

Genome annotation databases

EnsembliENST00000209728; ENSP00000209728; ENSG00000094804.
GeneIDi990.
KEGGihsa:990.
UCSCiuc002huj.1. human.

Polymorphism databases

DMDMi50400620.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77949 mRNA. Translation: AAB38317.1 .
AF022109 mRNA. Translation: AAC52071.1 .
AY150310 Genomic DNA. Translation: AAN10296.1 .
BC025232 mRNA. Translation: AAH25232.1 .
CCDSi CCDS11365.1.
RefSeqi NP_001245.1. NM_001254.3.
UniGenei Hs.405958.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2CCH X-ray 1.70 E/F 89-100 [» ]
2CCI X-ray 2.70 F/I 71-100 [» ]
4I5L X-ray 2.43 B/E 70-90 [» ]
4I5N X-ray 2.80 B/E 70-90 [» ]
ProteinModelPortali Q99741.
SMRi Q99741. Positions 279-320.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107426. 49 interactions.
DIPi DIP-28154N.
IntActi Q99741. 21 interactions.
MINTi MINT-1201847.
STRINGi 9606.ENSP00000209728.

Chemistry

ChEMBLi CHEMBL2311228.

PTM databases

PhosphoSitei Q99741.

Polymorphism databases

DMDMi 50400620.

Proteomic databases

MaxQBi Q99741.
PaxDbi Q99741.
PRIDEi Q99741.

Protocols and materials databases

DNASUi 990.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000209728 ; ENSP00000209728 ; ENSG00000094804 .
GeneIDi 990.
KEGGi hsa:990.
UCSCi uc002huj.1. human.

Organism-specific databases

CTDi 990.
GeneCardsi GC17P038443.
HGNCi HGNC:1744. CDC6.
HPAi HPA050114.
HPA054703.
MIMi 602627. gene.
613805. phenotype.
neXtProti NX_Q99741.
Orphaneti 2554. Ear-patella-short stature syndrome.
PharmGKBi PA26271.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1474.
GeneTreei ENSGT00530000063498.
HOGENOMi HOG000045316.
HOVERGENi HBG050860.
InParanoidi Q99741.
KOi K02213.
OMAi PYTRNQI.
OrthoDBi EOG7QG44J.
PhylomeDBi Q99741.
TreeFami TF101051.

Enzyme and pathway databases

Reactomei REACT_1095. Activation of the pre-replicative complex.
REACT_111214. G0 and Early G1.
REACT_1156. Orc1 removal from chromatin.
REACT_1181. Association of licensing factors with the pre-replicative complex.
REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
REACT_1707. CDC6 association with the ORC:origin complex.
REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
REACT_207. Removal of licensing factors from origins.
REACT_2243. Assembly of the pre-replicative complex.
REACT_471. E2F mediated regulation of DNA replication.
REACT_6769. Activation of ATR in response to replication stress.
REACT_683. G1/S-Specific Transcription.
SignaLinki Q99741.

Miscellaneous databases

ChiTaRSi CDC6. human.
EvolutionaryTracei Q99741.
GeneWikii CDC6.
GenomeRNAii 990.
NextBioi 4156.
PMAP-CutDB Q99741.
PROi Q99741.
SOURCEi Search...

Gene expression databases

Bgeei Q99741.
CleanExi HS_CDC6.
ExpressionAtlasi Q99741. baseline and differential.
Genevestigatori Q99741.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
3.40.50.300. 1 hit.
InterProi IPR003593. AAA+_ATPase.
IPR015163. Cdc6_C_dom.
IPR016314. Cell_div_Cdc6/18.
IPR027417. P-loop_NTPase.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view ]
Pfami PF09079. Cdc6_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF001767. Cdc6. 1 hit.
SMARTi SM00382. AAA. 1 hit.
SM01074. Cdc6_C. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase."
    Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A.
    Mol. Cell. Biol. 18:2758-2767(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PCNA; ORC1 AND CYCLIN-CDK.
  3. NIEHS SNPs program
    Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-238; ASN-295; MET-299; HIS-378 AND ILE-441.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-441.
    Tissue: Brain.
  5. "Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage."
    Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G.
    Mol. Biol. Cell 18:3340-3350(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUWE1.
  6. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  8. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-127, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  9. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. Cited for: VARIANT MGORS5 ARG-323.

Entry informationi

Entry nameiCDC6_HUMAN
AccessioniPrimary (citable) accession number: Q99741
Secondary accession number(s): Q8TB30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 1997
Last modified: November 26, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3